Psychological and methodological issues in substance abuse treatment/research are under investigation as part of the clinical trials evaluating cocaine and opioid abuse treatments. In addition to the projects below, research is underway to evaluate the relationships between HIV risk behaviors and HIV status and treatment outcome and methods for measuring craving. One area of interest is the identification of predictors of drug abuse treatment outcome. Intake variables from 96 polydrug users who had participated in voucher-based reinforcement therapy clinical trials were evaluated to determine which predicted clinically significant periods of abstinence. Logistic regression analysis revealed two significant pretreatment by study condition interactions: lower baseline use by voucher reinforcement therapy and non anti-social personality diagnoses by voucher reinforcement therapy. In a smaller subset of 19 subjects, drug use data collected during a 5-week baseline period were analyzed to evaluate its potential utility to predict treatment outcome. Cocaine use in the first and last baseline visit, first and last baseline week, and mean across the baseline was compared in subjects who responded with sustained abstinence and patients who did not. Overall, treatment responders used significantly less cocaine in baseline than non- responders; differences in cocaine use were not evident in the first visit or week, but were significant in the last visit and week of baseline. Cocaine use differentially changed during baseline: responders tended to decrease use across the baseline while non-responders tended to increase use over the same period. Further research is underway to identify risk typologies that could improve response to treatment for high baseline cocaine users and individuals diagnosed with anti-social personality disorder. Additional studies have focused on the specificity of familial transmission of alcohol and drug dependence and methods for monitoring cocaine use. Evaluation of the family histories of methadone maintenance patients enrolled in our clinical trials revealed that their parents and siblings had higher rates of drug and alcohol dependence than the general population. Evidence was found to support familial transmission of substance use disorder; however, transmission was not specific for alcohol or drugs. Differences between rates of transmission in males and females were noted. Virtually all commercial and investigational monitoring of cocaine use has been done by detecting the presence of the cocaine metabolite benzoylecognine in urine. Alternative methods of monitoring drug use are being evaluated.